Neuroblastoma, a common solid tumor of children, has been treated with limited success with cytotoxic chemotherapeutic drugs. It may spontaneously differentiate in vivo, perhaps preventing tumours from presenting themselves. In model studies, clonal mouse neuroblastoma cells grown in tissue culture with dibutyryl cAMP or other agents increasing intracellular cAMP levels are not only biochemically and morphologically differentiated but are less tumorigenic in the syngeneic Ajax mouse. We propose to investigate the correlation between differentiation, as evidenced by increases in the levels of specific markers including cAMP binding proteins, and their in vivo tumorigenicity. The transcriptional, translational and post-translational mechanisms will be studied including the effectors of transcriptional control, the nuclear acidic proteins and the changes in the synthesis and processing of m-RNAs. Control at the translational level will be studied by the analysis of levels of the in vivo synthesis of specific proteins, separated by two-dimensional gel electrophoresis, and extended by analysis of the levels of cytoplasmic messenger RNAs, assayed in in vitro protein synthesizing systems. We will also investigate the altered synthesis and/or glycosylation of membrane proteins as the direct modulators of tumorigenicity. Specific alterations which correlate with reduced tumorigenicity will define a system in which to predict and test new non-toxic drugs capable of differentiating neuroblastoma in vivo.